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Wang SP, Zang WJ, Kong SS, Yu XJ, Sun L, Zhao XF, Wang SX, Zheng XH: Vasorelaxant effect of isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate, a novel metabolite from Salvia miltiorrhiza, on isolated rat mesenteric artery. Eur J Pharmacol. 2008 Jan 28;579(1-3):283-8. Epub 2007 Oct 13.
The present study was designed to investigate the relaxant effect of isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), a new metabolite from Salvia miltiorrhiza, on rat mesenteric artery. Isolated mesenteric arterial rings were mounted in organ baths and the isometric tension changes were measured continuously by a sensitive myograph system. The results showed that IDHP at concentrations greater than 0.1 nM produced a concentration-dependent relaxation of artery contracted by norepinephrine with pEC (50) of 7.41+/-0.08. Removal of the endothelium did not affect this relaxation, suggesting that IDHP exerted a direct effect on vascular smooth muscle cells. Meanwhile, the vasorelaxant effect of IDHP was unaffected by pre-treatment with ATP-sensitive K (+) channel inhibitor glibenclamide, delayed rectifier K (+) channel inhibitor 4-aminopyridine, inwardly rectifying K (+) channel inhibitor barium chloride and beta-adrenoceptor antagonist propranolol. However, the non-specific K (+) channel inhibitor tetraethylammonium (TEA, 3 mM) produced a rightward shift of 1.8 fold on the concentration-response curve of IDHP. Moreover, IDHP shifted the concentration-response curve of CaCl (2) as well as two receptor-mediated constrictors, phenylephrine and 5-hydroxytryptamine, to the right in a non-parallel manner. In the absence of extracellular Ca (2+), IDHP depressed the contractions induced by norepinephrine and CaCl (2), and the maximal inhibitions were 48.3+/-18.9% and 58.4+/-10.9%, respectively. These results suggest that IDHP exerts a vasorelaxant effect by inhibiting both Ca (2+) release from intracellular stores and Ca (2+) influx through voltage-dependent calcium channels, and receptor-operated calcium channels in vascular smooth muscle cells. In addition, activation of vascular TEA-sensitive K (+) channels may be partially involved in the relaxant effect of IDHP. |
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